ABSTRACT All functions of the Protocol Review and Monitoring System (PRMS) fall within the scope of responsibility of the Cancer Protocol Committee (CPC). The CPC is a scientific peer-review committee comprised of 35 voting members that reflect the multidisciplinary clinical research enterprise at the DCI, and its operations are supported and monitored by three co-Chairs and four full-time employees. The CPC is responsible for evaluating the scientific merit, priority, and progress of all studies that meet the DCI definition of cancer- related. New cancer-related protocols must be approved by the CPC prior to activation, and most approved studies that remain open to enrollment must undergo continuing review by the CPC on at least an annual basis. The CPC approves well-designed studies that hold the potential to change cancer care, and it is authorized to terminate studies that fail to demonstrate meaningful progress or lose relevance due to shifting paradigms of cancer research and cancer patient care. The CPC is a key committee in the DCI protocol review process. It not only upholds standards in scientific rigor and integrity during the protocol review process, it also helps investigators and study teams attain such standards by providing essential resources and education. By meeting its scientific oversight responsibilities, the CPC ensures that DCI investigators conduct high quality and impactful clinical research that aligns with the DCI's research priorities and fulfills the needs of the cancer patient community.